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Progesterone supplementation to reduce the risk of spontaneous preterm birth

Errol R Norwitz, MD, PhD, MBA
Section Editor
Charles J Lockwood, MD, MHCM
Deputy Editor
Vanessa A Barss, MD, FACOG


Preterm birth (delivery prior to 37 weeks or 259 days of gestation) complicates 1 in 8 deliveries in the United States, but accounts for over 85 percent of all perinatal morbidity and mortality. Efforts to delay delivery in women presenting with acute preterm labor have been largely unsuccessful. For this reason, much attention has focused on preventive strategies, such as progesterone supplementation.

Although supplemental progesterone appears to be effective in preventing preterm birth in some high-risk women, it should not be seen as a panacea. For example, even if all pregnant women in the United States with a history of preterm birth receive progesterone prophylaxis, it is estimated that the risk of preterm birth would be reduced by 20 percent and the absolute preterm birth rate would be reduced by only 0.01 percent because most preterm births are not recurrences and prophylaxis has limited efficacy [1-4]. If women with a short cervix are also identified and treated, an additional absolute risk reduction of 0.02 percent would be achieved [4].

This topic will review issues related to use of progesterone for prevention of preterm birth. Progesterone supplementation is only one component of risk reduction. Risk factors for preterm birth and other potential interventions for reducing risk are discussed separately. (See "Preterm birth: Risk factors and interventions for risk reduction".)


Progesterone is a steroid hormone initially produced by the corpus luteum. In early pregnancy, progesterone is critical for pregnancy maintenance until the placenta takes over this function at 7 to 9 weeks of gestation, and its name is derived from this function: pro-gestational steroidal ketone. Indeed, removal of the source of progesterone (the corpus luteum) [5] or administration of a progesterone receptor antagonist [6] readily induces abortion before 7 weeks (49 days) of gestation.

Progesterone appears to be important in maintaining uterine quiescence in the latter half of pregnancy; however, the mechanism is unclear [7-9]. Functional withdrawal of progesterone activity at the level of the uterus appears to occur proximate to the onset of labor both at term and preterm, without a significant change in serum progesterone levels in the weeks preceding labor [7-14]. Progesterone also prevents apoptosis in fetal membrane explants under both basal and pro-inflammatory conditions [15,16] and thus may protect the membranes from preterm premature rupture and, in turn, preterm birth.

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Literature review current through: Sep 2017. | This topic last updated: Oct 03, 2017.
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